OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

italic>Fusarium oxysporum widely exists in farmland soil and is one of the main pathogenic fungi of root rot, which seriously affects the growth and development of plants and often causes serious losses of cash crops. In order to screen out natural compounds that inhibit the activity of Fusarium oxysporum more economically and efficiently, random forest, support vector machine and artificial neural network based on machine learning algorithms were constructed using the information of known inhibitory compounds in ChEMBL database in this study. And the antibacterial activity of the screened drugs was verified thereafter. The results showed that the prediction accuracy of the three models reached 77.58%, 83.03% and 81.21%, respectively. Based on the inhibition experiment, the best inhibition effect (MIC = 0.312 5 mg·mL^-1) of ononin was verified. The virtual screening method proposed in this study provides ideas for the development and creation of new pesticides derived from natural products, and the screened ononin is expected to be a potential lead compound for the development of novel inhibitors of Fusarium oxysporum.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.
Humans ; Practice Guidelines as Topic

BACKGROUND: Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up. METHODS: The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287 days in group A and 227 days in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student's t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DS ≥50%) at mid-term follow-up using the area under the curve (AUC). RESULTS: A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; P < 0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; P < 0.001). CONCLUSIONS The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.
Constriction, Pathologic ; Coronary Angiography ; Coronary Artery Disease/therapy* ; Coronary Restenosis ; Follow-Up Studies ; Fractional Flow Reserve, Myocardial ; Humans ; Pharmaceutical Preparations ; Predictive Value of Tests ; Retrospective Studies ; Treatment Outcome

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies. Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout. Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population. Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population. Clinical Trial Identifier NCT00856544 and NCT00413699.
Administration, Oral ; Adult ; Aged ; Arthritis, Rheumatoid ; drug therapy ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Middle Aged ; Piperidines ; adverse effects ; therapeutic use ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrimidines ; adverse effects ; therapeutic use ; Pyrroles ; adverse effects ; therapeutic use ; Surveys and Questionnaires ; Young Adult

BACKGROUNDApproximately 15-20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric-onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult-onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database.

METHODSWe made a prospective study of 225 cSLE patients (aged Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI], 0.470-0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512-2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053-2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170-0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log-rank test (0.557, P = 0.455).

CONCLUSIONScSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5- year survival between cSLE and aSLE groups.

Adolescent ; Adult ; Age Factors ; Age of Onset ; Child ; China ; epidemiology ; Female ; Humans ; Lupus Erythematosus, Systemic ; epidemiology ; mortality ; pathology ; Male ; Middle Aged ; Odds Ratio ; Proportional Hazards Models ; Prospective Studies ; Registries ; Severity of Illness Index ; Young Adult

Objective To evaluate the clinical efficacy and safety of memantine combined with olanzapine in treating Alzheimer's disease patients with behavioral and psychological symptoms of dementia (BPSD).Methods One hundred and seventy-six cases of Alzheimer's disease with BPSD were randomly divided into treatment group (n =87) and control group (n =89).The control group received oral administration of memantine 5-20 mg qd.The treatment group was given oral administration of olanzapine 2.5-10 mg qn on the basis of control group.The treatment course was two weeks.Both groups were treated for 6 courses.Clinical efficacy,neuropsychiatric inventory scale (NPI),activities of daily living (ADL) score,and the incidence of adverse drug reactions were compared between the two groups.Results After treatment,the total efficiency of the treatment group and the control group were 90.70％ (78/86 cases)and 75.29％ (64/85 cases) respectively,and the statistically significant difference was shown between the two groups (P＜0.01).Before treatment and at week 2,4,8,12,NPI-1 in the treatment group and were(25.18 ±4.17) (23.02 ± 3.98),(20.51 ± 3.65),(17.85 ± 3.08),(16.56 ± 2.95);NPI-2 were (46.86 ± 4.65) (45.78 ± 4.62),(43.53 ± 4.24),(40.53 ± 4.31),(38.91 ± 4.27);ADL were (44.34 ± 4.59),(44.25 ± 4.53) (42.85 ±4.01),(40.30 ± 3.98),(39.21 ± 3.48).NPI-1 in the control group were(25.27 ±4.23) (24.67 ±4.12),(23.68 ± 3.98),(21.36 ± 3.57),(19.92 ± 3.24);NPI-2 were (46.56 ± 4.72) (46.31 ± 4.51),(45.82 ± 4.42),(43.21 ± 4.37),(42.74 ± 4.33);ADL were (43.62 ± 4.61),(43.36 ± 4.49) (43.08 ±4.25),(42.18 ±4.31),(41.27 ±4.29).Statistical significant differences were found in NPI-1,NPI-2 and ADL between the two groups at week 2,4,8(P ＜0.01).The adverse drug reactions in the treatment group were hypersomnia,weight gain,dry mouth and constipation;and dizziness,sleeplessness,headache,nausea in the control group.The incidence of adverse drug reactions in treatment and control groups were 8.14％ (7/86 cases) and 7.06％ (6/85 cases),without statistically significant difference (P ＞ 0.05).Conclusion Memantine combined with olanzapine achieves better efficacy than memantine alone in treating patients with Alzheimer's disease and BPSD.

Background: Approximately 15–20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric?onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult?onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database. Methods: We made a prospective study of 225 cSLE patients (aged <16 years) and 1759 patients aged 16–50 years based on CSTAR registry. We analyzed initial symptoms, clinical presentations, SLE disease activity, damages, and outcomes of cSLE, as well as compared with aSLE patients. Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI ], 0.470–0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512–2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053–2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170–0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log?rank test (0.557, P = 0.455). Conclusions: cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5? year survival between cSLE and aSLE groups.

OBJECTIVETo know how Shenfu injection is used in clinical practice and to provide a reference for guiding clinical use of Shenfu injection.

METHODExtract Shenfu injection's post-marketing re-evaluation data from the hospital information system (HIS) of 20 national grade III-A General Hospitals, use basic statistical analysis methods to analyze Shenfu injection's indications, usage and dosage, treatment course etc. in clinical practice.

RESULTIn patients using Shenfu injection, the average age was 62. 15, and patients mainly concentrated in cardiovascular medicine. In clinical practice, Shenfu injection was used mainly for treatment of coronary heart disease (diagnosed as chest obstruction in traditional Chinese medicine). The treatment course mainly ranged from 3 to 7 days, and the dosage was within the limits prescribed by the instruction.

CONCLUSIONShenfu injection was mainly used for elderly patients, and has been used according to instruction in practice almostly.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Clinical Trials as Topic ; Databases, Factual ; Drug Therapy ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hospital Information Systems ; Humans ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Young Adult

OBJECTIVETo summarize lessons learned from an outbreak of severe acute respiratory syndrome (SARS) in China during the spring of 2004.

METHODSData of SARS cases were officially reported by Beijing Municipal Center for Disease Control and Prevention (BCDC) and Anhui Provincial Center for Disease Control and Prevention (APCDC) and results of epidemiological investigations were collected and analyzed.

RESULTSThree generations of 11 cases of SARS were identified during the outbreak. Initial two cases were most likely to be infected in Diarrhea Virus Laboratory of National Institute of Virology, China Centers for Disease Control and Prevention and main mode of transmission was direct contact with SARS patients. Delay in detecting initial case resulted in spread of the illness at hospitals and communities with two generations of secondary cases.

CONCLUSIONSSARS outbreak in 2004 has yielded following lessons for public health globally. (1) Lab bio-safety programs should be made and should be strictly abided by. Studies in highly pathogenic viruses such as SARS coronavirus should be utmost cautious. (2) Management systems of occupational exposure to virus and disease surveillance need to be strengthened to take all risk factors into account so as to detect potential patients with infectious disease as early as possible.

China ; epidemiology ; Disease Outbreaks ; Female ; Humans ; Male ; Occupational Exposure ; prevention & control ; Occupational Health ; Retrospective Studies ; Severe Acute Respiratory Syndrome ; epidemiology ; prevention & control ; transmission